Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells
Growth inhibitory effect of paratocarpin E, a prenylated chalcone isolated from Euphorbia humifusa Wild., by induction of autophagy and apoptosis in human breast cancer cells
复制标题
DOI：
10.1016/j.bioorg.2016.10.005
复制
发表时间：
2016-12-01
影响因子：
5.1
通讯作者：
Chen, Lixia
中科院分区：
文献类型：
--
作者：
Gao, Suyu;Sun, Dejuan;Chen, Lixia
从胡麻中分离得到5个黄酮类化合物，包括4个黄酮类化合物和1个异戊烯基查尔酮(副果苷E)。并通过光谱分析确定了它们的化学结构。我们评估了这些化合物对人类乳腺癌、白血病和肾癌细胞系生长的有效性。其中，类胡萝卜素E对这些癌细胞具有明显的细胞毒作用，其对MCF-7细胞生长的IC50为19.6mU/L。副果苷E处理MCF-7细胞后，通过增加活化的caspase-8和-9的表达和PARP的裂解，导致典型的细胞凋亡特征。此外，副果皮苷E改变了Bax和Bcl2的表达，导致细胞色素c从线粒体释放到胞浆中，表明线粒体介导的细胞凋亡已经启动。此外，副果胶E还能增加MDC阳性的自噬空泡，增加Beclin-1的Lc3-II/Lc3-I蛋白水平，但降低p62的表达，表明副果皮素E对MCF-7细胞具有较强的促自噬作用。从机制上讲，副果皮素E诱导的细胞死亡可以通过激活p38和JNK信号通路，抑制Erk通路，从而诱导MCF-7细胞的凋亡。此外，副果皮素E促进核因子-kappaB的激活和核转位，在平衡副果皮素E介导的细胞凋亡和自噬中起着重要作用。分子对接研究还表明副果苷E与Fas和核因子-kappaB复合体结合。这些发现提供了初步证据，表明副果苷E可以作为一种潜在的抗癌药物用于乳腺癌的治疗。(C)2016 Elsevier Inc.保留所有权利。
Five flavones, including four flavonoids and one prenylated chalcone (paratocarpin E), were isolated from E. humifusa. and their chemical structures were established by spectroscopic analyses. We assessed the efficacy of these compounds against the growth of human breast cancer, leukemic, kidney cancer cell lines. Among them, paratocarpin E showed significant cytotoxicity against these cancer cell lines with an IC50 of 19.6 mu M on the growth of MCF-7 cells. Paratocarpin E treatment of MCF-7 cells resulted in typical apoptotic features via increasing expression of activated caspase-8 and -9 and PARP cleavage. Moreover, paratocarpin E altered the expression of Bax and Bcl-2, leading to the release of cytochrome c from the mitochondria into the cytosol, suggesting that the mitochondria-mediated apoptosis was initiated. In addition, paratocarpin E increased the MDC-positive autophagic vacuoles, the ratio of LC3-II/LC3-I protein levels of Beclin-1, but decreased p62 expression, indicating the potent pro-autophagic effects of paratocarpin E in MCF-7 cells. Mechanistically, cell death induced by paratocarpin E is able to induce apoptosis of MCF-7 cells by activating p38 and JNK signaling pathway while inhibiting Erk pathway. Furthermore, paratocarpin E promotes the activation and nuclear translocation of NF-kappa B, which plays an important role in balancing paratocarpin E-mediated apoptosis and autophagy. The molecular docking study also revealed that paratocarpin E bound to Fas and NF-kappa B complex. These findings provide initial evidences that paratocarpin E can be used as a potential anti-cancer drug in future for breast cancer therapy. (C) 2016 Elsevier Inc. All rights reserved.